Maintenance of functional status, the prevention of comorbidity and continued health after retirement are major challenges facing the older population. Advances in these fields require study of factors over the life course; however, few studies have such data. The Johns Hopkins Precursors Study, begun in 1946, is a long-term prospective study of 1,337 former Johns Hopkins medical students. The overall hypothesis being tested is that the process of aging is an interactive function of psychologic, physiologic, social, and behavioral characteristics over the life course. The study is unique in having prospectively collected data on these factors in this cohort from young adulthood to late middle age. Data on over 6,000 variables were collected in medical school, at an average age of 22 years, and the cohort has been followed by annual questionnaires. The response rate over this long follow-up is very high and these former medical students have been demonstrated to be accurate in the reporting of exposures and disease endpoints. The average age of the participants is now 60 years, providing a window of opportunity in the life of the cohort to study the onset of functional limitation and the relationship of retirement to health. The specific aims of this phase of the study are: 1) to continue the longitudinal description of the onset of disease and death in this cohort; 20 to determine the association of psychologic, physiologic, social and health behavioral factors, assessed over the life course, with later disease, and death; the level of risk associated the timing, strength, and duration of exposure will also be determined; 30 to assess the decline in health status as this cohort ages and the influence of impairments (chronic diseases and other condiitons of aging) and comorbidity on this decline; 40 to investigate the influence of the psychosocial work environment in midlife on future health and functional status and retirement; and, 5) to measure the effect of specific life events, especially retirement, on subsequent psychological and physical health and functional status. The results of the proposed work will identify a multi-factorial risk profile of groups at risk for development of disease at older ages, functional decline, and poor outcomes after retirement. Thousands of person-years of work and millions of dollars of support have contributed to the study over the last 46 years, enabling insights into the risk of disease in midlife associated with exposures early in life. The study is now poised to make a similar contribution to older age groups.